Partial recovery of senescence and differentiation disturbances in CD8(+) T cell effector-memory cells in HIV-1 nfection after initiation of anti-retroviral treatment.
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Partial recovery of senescence and differentiation disturbances in CD8(+) T cell effector-memory cells in HIV-1 nfection after initiation of anti-retroviral treatment. / Eberhard, Johanna Maria; Ahmad, Fareed; Hong, Henoch S; Bhatnagar, Nupur; Keudel, Phillip; Schulze zur Wiesch, Julian; Schmidt, Reinhold E; Meyer-Olson, Dirk.
in: CLIN EXP IMMUNOL, Jahrgang 186, Nr. 2, 11.2016, S. 227-238.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Partial recovery of senescence and differentiation disturbances in CD8(+) T cell effector-memory cells in HIV-1 nfection after initiation of anti-retroviral treatment.
AU - Eberhard, Johanna Maria
AU - Ahmad, Fareed
AU - Hong, Henoch S
AU - Bhatnagar, Nupur
AU - Keudel, Phillip
AU - Schulze zur Wiesch, Julian
AU - Schmidt, Reinhold E
AU - Meyer-Olson, Dirk
N1 - © 2016 British Society for Immunology.
PY - 2016/11
Y1 - 2016/11
N2 - BACKGROUND: Immune senescence as well as disturbed CD8(+) T cell differentiation are a hallmark of chronic HIV infection. Here, we investigated to what extent immune senescence is reversible after initiation of antiretroviral treatment (ART).METHODS: PBMCs from a cohort of HIV patients with different disease courses including untreated viral controllers (n=10), viral non-controllers (n=16) and patients on anti-retroviral therapy (ART) (n=20), were analyzed and compared to uninfected controls (n=25) by flow cytometry on bulk and HIV-specific MHC class I tetramer(+) CD8(+) T cells for expression of the memory markers CCR7, CD45RO, as well as the senescence marker CD57 and the differentiation and survival marker CD127. Furthermore, a subset of patients was longitudinally analyzed before and after initiation of ART.RESULTS: Frequencies of CD57(+) CD8(+) T cells decreased after initiation of ART in central (Tcm) but not in effector memory (TemRO and TemRA) populations. The frequency of CD127(+) CD8(+) cells increased in Tcm and TemRO. We observed a reduction of CD127(-) T cells in Tcm, TemRO and partially in TemRA subsets after initiation of ART. Importantly, HIV-specific CD8(+) TemRO cells predominantly displayed a CD127(-) CD57(+) phenotype in untreated HIV-patients, whereas the CD127(+) CD57(-) phenotype was underrepresented in these patients. The frequency of the CD127(+) CD57(-) CD8(+) T cell subpopulation strongly correlated with absolute CD4(+) counts in HIV-infected patients before and after initiation of ART.CONCLUSIONS: These findings can be interpreted as phenotypical correlate of CD8(+) memory T cell differentiation and the premature 'aging' of the immune system, which was even observed in successfully virally suppressed ART HIV patients. This article is protected by copyright. All rights reserved.
AB - BACKGROUND: Immune senescence as well as disturbed CD8(+) T cell differentiation are a hallmark of chronic HIV infection. Here, we investigated to what extent immune senescence is reversible after initiation of antiretroviral treatment (ART).METHODS: PBMCs from a cohort of HIV patients with different disease courses including untreated viral controllers (n=10), viral non-controllers (n=16) and patients on anti-retroviral therapy (ART) (n=20), were analyzed and compared to uninfected controls (n=25) by flow cytometry on bulk and HIV-specific MHC class I tetramer(+) CD8(+) T cells for expression of the memory markers CCR7, CD45RO, as well as the senescence marker CD57 and the differentiation and survival marker CD127. Furthermore, a subset of patients was longitudinally analyzed before and after initiation of ART.RESULTS: Frequencies of CD57(+) CD8(+) T cells decreased after initiation of ART in central (Tcm) but not in effector memory (TemRO and TemRA) populations. The frequency of CD127(+) CD8(+) cells increased in Tcm and TemRO. We observed a reduction of CD127(-) T cells in Tcm, TemRO and partially in TemRA subsets after initiation of ART. Importantly, HIV-specific CD8(+) TemRO cells predominantly displayed a CD127(-) CD57(+) phenotype in untreated HIV-patients, whereas the CD127(+) CD57(-) phenotype was underrepresented in these patients. The frequency of the CD127(+) CD57(-) CD8(+) T cell subpopulation strongly correlated with absolute CD4(+) counts in HIV-infected patients before and after initiation of ART.CONCLUSIONS: These findings can be interpreted as phenotypical correlate of CD8(+) memory T cell differentiation and the premature 'aging' of the immune system, which was even observed in successfully virally suppressed ART HIV patients. This article is protected by copyright. All rights reserved.
U2 - 10.1111/cei.12837
DO - 10.1111/cei.12837
M3 - SCORING: Journal article
C2 - 27377704
VL - 186
SP - 227
EP - 238
JO - CLIN EXP IMMUNOL
JF - CLIN EXP IMMUNOL
SN - 0009-9104
IS - 2
ER -